Is PEX1 p.Leu910fs (c.2730del) pathogenic?

PEX1 p.Leu910fs (c.2730del) is classified Pathogenic in PEX1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00119%, nfe); Associated with PEX1-related disorder.

What condition is associated with PEX1 p.Leu910fs (c.2730del)?

PEX1 p.Leu910fs (c.2730del) is associated with PEX1-related disorder, peroxisome biogenesis disorder 1A (Zellweger), inherited retinal dystrophy (ClinVar).

How common is PEX1 p.Leu910fs (c.2730del) in the general population?

PEX1 p.Leu910fs (c.2730del) is very rare (popmax 0.00119%, nfe) (gnomAD).

PEX1 p.Leu910fs

c.2730del · rs61750423 · VCV188971

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Conditions

PEX1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 4, phastCons 1
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,173,354 alleles

Filtering AF 0.000692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000542%

Overall 0.000871% 14/1,606,476 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PEX1
Protein: p.Leu910fs
Coding: c.2730del
MANE Select: NM_000466
dbSNP: rs61750423
Type: Deletion
Location: chr7:92496766 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 910: a UniProt-annotated variant site (in pbd1a)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PEX1-related disorder

Also linked: peroxisome biogenesis disorder 1A (Zellweger)inherited retinal dystrophy peroxisome biogenesis disorder Zellweger spectrum disorders

Similar variants

PEX1 c.2072-42_2085del Likely pathogenic ★★ same condition
PEX1 p.Ala15fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ala921fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg1208fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg827fs Pathogenic ★★ same condition
PEX1 p.Asn1088fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Asn403fs Pathogenic ★★ same condition
PEX1 p.Asp378fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pex1-p-leu910fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown